It is known that various immunomodulatory factors (also referred to as lymphokines) are produced by human T cells, and some of these immunomodulatory factors are present as factors possessing immunosuppressive activity by which immune response is attenuated.
For example, Schnaper et al. reported that a factor possessing suppressive activity on polyclonal antibody production by human B cells stimulated with pokeweed mitogen (soluble immune response suppressor: SIRS) is produced as an immunosuppressive factor derived from human T cells in culture supernatant by stimulated human spleen cells (specifically OKT 8 positive suppressor T cells) with concanavalin A [J. Immunol., vol. 132, p. 2429(1984)]. The factor SIRS has a molecular weight of 110,000 to 150,000; it is inactivated by pH 3 treatment; it is activated by oxidizing agents such as hydrogen peroxide; it is inactivated by reducing agents such as 2-mercaptoethanol.
Greene et al. reported that a factor possessing suppressive activity on blastogenesis of human T cell by phytohemagglutinin stimulation (soluble immune suppressor supernatant of T cell proliferation SISS-T) and another factor which suppresses polyclonal antibody production by human B cells stimulated with pokeweed mitogen (soluble immune suppressor supernatant of B cell immunoglobulin production: SISS-B) are produced from human peripheral blood lymphocytes stimulated by concanavalin A. It was demonstrated that the factor SISS-T has a molecular weight of 30,000 to 45,000, whose activity is inhibited bY addition of N-acetyl-Dglucosamine, and the factor SISS-B has a molecular weight of 60,000 to 80,000, whose activity is inhibited by addition of L-rhamnose [J. Immunol., vol. 126, p. 1185 (1981)].
In addition, it was reported that factors possessing suppressive activities on immune reaction are produced from various T cell lines such as T cell leukemia cells, as well as normal human T cells. For example, as a factor derived from human leukemia cells, Catharine et al. reported that a factor which activates suppressor T cells (suppressor-activating factor: SAF), is produced by 6-thioguanine-resistant human T cell leukemia cell CCRF-CEM [J. Immunol., vol. 134, p. 3155 (1985)-. Santoli et al. found that a factor which suppresses proliferation of human leukemia cells themselves (T leukemia-derived suppressor lymphokine: TLSL) is produced from human T cell leukemia cells such as CCRF-CEM and HUT-78 [J. Exp. Med., vol. 163, p. 18 (1986)]. Moreover, Hersey et al. found that factors which have a molecular weight of 44,000 or 7,000 and which specifically suppress production of interleukin 2 by T cells are produced by melanoma cells LJ. Immunol., vol. 131, p. 2837 (1983)-, and it was reported by Fontana et al. that a factor which has a molecular weight of 97,000 and which suppresses proliferation of interleukin 2dependent T cells is produced by human neuroglioblastoma cells [J. Immunol., vol. 132, p. 1837 (1984)].
In addition, Hashimoto et al. found that, when human peripheral blood lymphocytes are stimulated with concanavalin A, a factor which suppresses DNA synthesis in various cells (stimulated T cell derived inhibitory factor for cellular DNA synthesis: STIF) is produced. It was demonstrated that the factor STIF is a factor of protein nature having a molecular weight of 45,000 to 65,000 and an isoelectric point of 4.5 to 5.5, and it is produced by OKT 8 positive suppressor T cells.